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Coenzyme Q with a vanilla flavor


The primary coenzyme Q deficiency causes severe pathologies in humans. In a recent study, Chemistry and Biology of Metals laboratory researchers showed that synthetic analogues of the precursor of the aromatic ring of Q, could also serve as precursors for the Q biosynthesis which opens new perspectives for human therapy.​

Published on 26 January 2012

Coenzyme Q (ubiquinone or Q) is a redox lipid which structure was established in 1958. Q is essential for ATP synthesis in eukaryotes because of its crucial role as an electron shuttle in the mitochondrial respiratory chain. Primary coenzyme Q deficiencies results from mutations in Q biosynthetic genes and causes severe pathologies [1].

Q biosynthesis is conserved from bacteria to humans with minor differences and necessitates 9 reactions. Most proteins responsible for these chemical reactions have been identified by genetic studies on model micro-organisms like the yeast Saccharomyces cerevisiae and the bacterium Escherichia coli. In addition, several genes are known to be essential for Q biosynthesis but the function of the encoded proteins is still unknown and more genes are likely to be discovered.

Researchers from our laboratory use S. cerevisiae as a model organism to better characterize the Q biosynthetic pathway. Their results have established that the protein Coq6, which is proposed to be a flavin-dependent mono-oxygenase, is implicated in only 1 of the 3 hydroxylation reactions which are necessary for Q biosynthesis [2]. Flavin-dependant mono-oxygenases usually use NADH/NADPH as a reductant. Surprisingly, the mitochondrial ferredoxin Yah1 and the ferredoxin reductase Arh1 are also essential for the hydroxylation reaction catalyzed by Coq6 [3]. This result suggests that Yah1 and Arh1 may provide electrons for reducing the flavin cofactor of Coq6 and this hypothesis is presently tested in the laboratory.

In the same study, the researchers have shown that synthetic analogs of 4-hydroxybenzoic acid (4-HB), the precursor of the aromatic ring of Q (Figure), can also be used by yeast as precursors for Q biosynthesis. One of these 4-HB analogs, vanillic acid, possesses a methoxy group at position C5 and was able to restore Q biosynthesis in a yeast strain mutated for coq6 which is therefore deficient for the C5-hydroxylation.


The length of the isoprenyl chain varies among organisms: n= 6 in the yeast Saccharomyces cerevisiae (Q6), 8 in Escherichia coli (Q8), 10 in humans (Q10). Endogenous 4-hydroxybenzoic acid (4-HB) is metabolized into coenzyme Q in the mitochondrial matrix by a complex which brings together most of the proteins implicated in Q biosynthesis in yeast. Mutation of one protein of the complex (Coq6 in the figure) causes a deficiency in Q. By providing exogenous vanillic acid (VA), it is possible to bypass the deficiency in the C5-hydroxylation reaction in yeast coq6 mutants and to restore Q biosynthesis in the mutant strains.


In 2011, COQ6 was the sixth gene of Q biosynthesis to be described as pathogenic when mutated. Patients with primary Q deficiency are presently treated by oral supplementation with coenzyme Q but the bioavailability of Q is problematic because of its high hydrophobicity.

The results obtained in yeast demonstrate the possibility of restoring Q biosynthesis with synthetic analogs of 4-HB which have the advantage of being hydrophilic compared to Q. Therefore, the use of 4-HB analogs opens new perspectives in the treatment of primary Q deficiency.





Redox lipid. The polyprenyl chain of Q confers a hydrophobic character to the molecule. Q has the capacity to exchange 2 electrons and 2 protons between its reduced and oxidized forms and is implicated in transferring electrons in the respiratory chain.

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